Dopamine-2 receptor blockade potentiates the renal effects of nitric oxide inhibition in humans.
In eight young healthy subjects on a 240 mM Na diet mean arterial pressure (MAP), renal hemodynamics and renal handling of Na and exogenous Li were measured at baseline and during acute nitric oxide (NO) inhibition with 90-minute infusion of 3.0 microg/kg x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The same experiment was repeated with infusion of 50 microg/kg x min(-1) of DA2 receptor blocker L-Sulpiride (L-SULP) alone and, finally, with simultaneous infusion of both L-NAME and L-SULP. L-SULP alone did not elicit any effect. L-NAME alone produced no changes in MAP from 0 to 45 minutes (P1) and a 6.6% increase at 45 to 90 minutes (P2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 10.2% and 7.6%, respectively, in P1 and by 15.3% and 11.5% in P2. Filtration Fraction (FF) rose by 4.2% in P2. Calculated renal vascular resistance (RVR) increased by 13.0% to 25.6%. Fractional excretion of Na (FENa) and Li (FELi) fell by 20.0% and by 16.0%, respectively, in P1 and by 40.0% and 25.1% in P2. All these variations, except for MAP and GFR, were significantly greater during coinfusion of L-NAME and L-SULP. ERPF declined by 17.8% to 33.7%, FENa by 26.7% to 53.3%, FELi by 13.8% to 34.8%, while RVR rose by 22.5% to 59.1% and FF by 10.1% to 29.3%. The present data confirm that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR with slight increase in FF, and enhanced tubular Li, and Na reabsorption. Since increase in RVR and FF and decrease in FENa and FELi are markedly potentiated by the simultaneous infusion of DA2 blocker L-SULP, which exerts no effects by itself, we suggest that DA interactions between DA system at the level of DA2 receptors and basal NO production play a physiological role in the regulation of renal function in humans.
Montanari
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Istituto di Patologia Medica, University of Parma, Italy. montalbr@ipruniv.cce.unipr.it
Tateo
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Fasoli
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Donatini
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Cimolato
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Perinotto
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Dall'Aglio
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D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009566:Nitrates / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000652:urine; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D012982:Sodium, Dietary; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D017447:Receptors, Dopamine D1; D012982:Sodium, Dietary; D013469:Sulpiride; D008094:Lithium; D012964:Sodium; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester